Development of new molecules often requires testing in different animal models and it is indispensable to evaluate their effects on the corresponding target receptors. In the case of the 5HT₃ receptor it was necessary to test the effects of a reference compound MKC-733 at the human, dog and ferret receptors. For this purpose we designed the corresponding 5HT₃ receptors from these three species based on our knowledge of the respective genomes. Sequence alignments between the three corresponding proteins highlight the numerous similitudes and differences in the sequences.

As it was shown that exchange of a single amino acid residues in critical protein region can cause functional differences it is expected that the 5HT₃ receptors from human, dog and ferret are likely to display physiological and pharmacological differences. Synthetic genes, designed in our laboratories, were tested using expression in Xenopus oocytes and we were able to show that 5HT₃ receptors from human significantly differ from those of dog or ferret. These data illustrate the relevance of testing compound at the proper receptor subtype.